Indian J Pediatr DOI 10.1007/s12098-014-1390-y
ORIGINAL ARTICLE
Effect of Short Term Zinc Supplementation on Iron Status of Children with Acute Diarrhea Zeeba Zaka-ur-Rab & Syed Moiz Ahmad & Mohammed Naim & Seema Alam & Mohammad Adnan
Received: 19 June 2012 / Accepted: 25 February 2014 # Dr. K C Chaudhuri Foundation 2014
Abstract Objective To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. Methods This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. Results Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p>0.05) was observed in mean hemoglobin (from 8.95±1.4 to 8.73± 1.43 g/dL), serum iron (79.56±45.81 to 78.61±44.41 μg/dL) and ferritin (84.77±45.35 to 83.55±44.10 ng/mL) levels. Total iron binding capacity increased from 331.60±109.72 to 341.30± 119.90 μg/dL post supplementation (p>0.05). Conclusions Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes. Keywords Children . Diarrhea . Zinc . Iron status Z. Zaka-ur-Rab (*) : S. M. Ahmad : S. Alam : M. Adnan Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002, India e-mail: [email protected] M. Naim Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
Introduction Diarrheal disorders account for a large proportion of morbidity and mortality in children under 5 y of age, especially in developing countries where more than 700 million episodes of diarrhea occur annually as per World Health Organization (WHO) [1]. On an average, children experience 3.2 episodes of diarrhea per year, the figure reaching 12 episodes per year per child in certain settings in some of these countries [2]. In view of the fact that dietary deficiency of zinc tends to be highly prevalent among preschool children from developing countries, and that there is increasing recognition of the role of zinc in diarrhea, WHO recommends that all children with acute diarrhea in at risk areas should receive oral zinc for 10/ 14 d for reducing both severity and duration of diarrhea [3]. Since both iron and zinc commonly co-exist in food, marginal iron and zinc status are usually associated, particularly in regions where diets are mainly vegetarian, with very little or no meat or dairy products whatsoever, but high phytate contents. Both these minerals being in the first transition series of periodic table have identical outer electronic shell configurations. The theorem of Hill and Matrone [4], on trace elements interactions states that, “those elements whose physiologic and chemical properties are similar will act antagonistically to each other biologically.” It has also been proposed that chemically similar ions could compete for some positions in a common absorptive pathway [5]. A high concentration of zinc or iron could, therefore, theoretically inhibit the absorption of each other. Data on interactions between the two, however, is confusing and published results are often contradictory. Whereas several researchers [6–16], have endeavored to investigate the effect of long term zinc supplementation (either alone or in combination with iron) on biochemical indicators of iron status, extensive search of published literature failed to reveal any convincing studies on effect of short term (2 wk)
Indian J Pediatr
zinc supplementation on iron status of children with acute diarrhea. The present study was, therefore, under taken to study the effect of short term (2 wk) oral zinc supplementation (10/20 mg/d) on hemoglobin and iron status of such children (3–60 mo age group).
Material and Methods This prospective interventional study was conducted from June 2008 through October 2009 in Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India, on 3 – 60-mo-old children with acute diarrhea. Patients with persistent or chronic diarrhea, dysentery, other acute or chronic infections, renal disorders, hemolytic anemias, severe anemia requiring blood transfusion, and recipients of zinc/ iron/ multivitamin/ mineral supplements/ herbal medications/ antibiotics within the past 6 wk were excluded from the study. Informed written consent was obtained from the guardians of patients. The research protocol was approved by the Institutional Ethics Committee. Considering probability of type I error (α)=0.05, desired power=0.8 a sample size of 49 (based on results of a pilot study conducted by the authors) was calculated to be sufficient to detect a difference of 5 ng/mL and 0.5 g/dL, respectively between the baseline and endline levels of ferritin and hemoglobin. However, keeping a possibility of 10 % drop out (including lost to follow-up), the sample size necessary to achieve the pre-specified α level and power was 60. The number of children who eventually completed the study exceeded the calculated sample size requirements for all principal outcomes. Children whose weight-for-height was below −3 SD or less than 70 % of the median WHO reference values or who had symmetrical edema involving at least the feet were classified as severely malnourished, whereas those with weight-forheight >−2 SD or ≥80 % were considered as having no or mild malnutrition [17, 18]. All consecutive patients with diarrhea (irrespective of severity of presentation) seeking hospital treatment were evaluated initially for inclusion in the study. Seventy five patients were selected using a random number table from amongst those fulfilling the criteria for inclusion (by personnel not involved in caring for the participants). Dehydration was managed as per WHO guidelines, and all subjects were administered oral zinc gluconate supplements (10 mg and 20 mg elemental zinc, respectively for children
ORIGINAL ARTICLE
Effect of Short Term Zinc Supplementation on Iron Status of Children with Acute Diarrhea Zeeba Zaka-ur-Rab & Syed Moiz Ahmad & Mohammed Naim & Seema Alam & Mohammad Adnan
Received: 19 June 2012 / Accepted: 25 February 2014 # Dr. K C Chaudhuri Foundation 2014
Abstract Objective To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. Methods This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. Results Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p>0.05) was observed in mean hemoglobin (from 8.95±1.4 to 8.73± 1.43 g/dL), serum iron (79.56±45.81 to 78.61±44.41 μg/dL) and ferritin (84.77±45.35 to 83.55±44.10 ng/mL) levels. Total iron binding capacity increased from 331.60±109.72 to 341.30± 119.90 μg/dL post supplementation (p>0.05). Conclusions Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes. Keywords Children . Diarrhea . Zinc . Iron status Z. Zaka-ur-Rab (*) : S. M. Ahmad : S. Alam : M. Adnan Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002, India e-mail: [email protected] M. Naim Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
Introduction Diarrheal disorders account for a large proportion of morbidity and mortality in children under 5 y of age, especially in developing countries where more than 700 million episodes of diarrhea occur annually as per World Health Organization (WHO) [1]. On an average, children experience 3.2 episodes of diarrhea per year, the figure reaching 12 episodes per year per child in certain settings in some of these countries [2]. In view of the fact that dietary deficiency of zinc tends to be highly prevalent among preschool children from developing countries, and that there is increasing recognition of the role of zinc in diarrhea, WHO recommends that all children with acute diarrhea in at risk areas should receive oral zinc for 10/ 14 d for reducing both severity and duration of diarrhea [3]. Since both iron and zinc commonly co-exist in food, marginal iron and zinc status are usually associated, particularly in regions where diets are mainly vegetarian, with very little or no meat or dairy products whatsoever, but high phytate contents. Both these minerals being in the first transition series of periodic table have identical outer electronic shell configurations. The theorem of Hill and Matrone [4], on trace elements interactions states that, “those elements whose physiologic and chemical properties are similar will act antagonistically to each other biologically.” It has also been proposed that chemically similar ions could compete for some positions in a common absorptive pathway [5]. A high concentration of zinc or iron could, therefore, theoretically inhibit the absorption of each other. Data on interactions between the two, however, is confusing and published results are often contradictory. Whereas several researchers [6–16], have endeavored to investigate the effect of long term zinc supplementation (either alone or in combination with iron) on biochemical indicators of iron status, extensive search of published literature failed to reveal any convincing studies on effect of short term (2 wk)
Indian J Pediatr
zinc supplementation on iron status of children with acute diarrhea. The present study was, therefore, under taken to study the effect of short term (2 wk) oral zinc supplementation (10/20 mg/d) on hemoglobin and iron status of such children (3–60 mo age group).
Material and Methods This prospective interventional study was conducted from June 2008 through October 2009 in Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India, on 3 – 60-mo-old children with acute diarrhea. Patients with persistent or chronic diarrhea, dysentery, other acute or chronic infections, renal disorders, hemolytic anemias, severe anemia requiring blood transfusion, and recipients of zinc/ iron/ multivitamin/ mineral supplements/ herbal medications/ antibiotics within the past 6 wk were excluded from the study. Informed written consent was obtained from the guardians of patients. The research protocol was approved by the Institutional Ethics Committee. Considering probability of type I error (α)=0.05, desired power=0.8 a sample size of 49 (based on results of a pilot study conducted by the authors) was calculated to be sufficient to detect a difference of 5 ng/mL and 0.5 g/dL, respectively between the baseline and endline levels of ferritin and hemoglobin. However, keeping a possibility of 10 % drop out (including lost to follow-up), the sample size necessary to achieve the pre-specified α level and power was 60. The number of children who eventually completed the study exceeded the calculated sample size requirements for all principal outcomes. Children whose weight-for-height was below −3 SD or less than 70 % of the median WHO reference values or who had symmetrical edema involving at least the feet were classified as severely malnourished, whereas those with weight-forheight >−2 SD or ≥80 % were considered as having no or mild malnutrition [17, 18]. All consecutive patients with diarrhea (irrespective of severity of presentation) seeking hospital treatment were evaluated initially for inclusion in the study. Seventy five patients were selected using a random number table from amongst those fulfilling the criteria for inclusion (by personnel not involved in caring for the participants). Dehydration was managed as per WHO guidelines, and all subjects were administered oral zinc gluconate supplements (10 mg and 20 mg elemental zinc, respectively for children
